Pharmacogenomics in Psychiatric Disorders

Abstract

The broad arsenal of psychotropic medications is characterised by significant interindividual variability in clinical response and adverse effects, stringent monitoring requirements, potential drug-drug interactions, difficult long-term adherence and high costs. Pharmacogenomics investigates the correlation between genetic polymorphisms and responsiveness to drugs and could provide a valuable guide to fulfill the promise of personalized therapy in the context of the genomic medicine era, by tailoring treatment based on the patient’s specific genetic markers. The present paper overviews the current advances in the clinical applications of pharmacogenomics to individualized psychotropic therapy.

Material and methods. The relevant recent pharmacogenomics literature is selected and analysed in order to illustrate the impact on the clinical outcomes and quality of life in psychiatric patients of the genetic variants in the neurotransmitter receptors (dopamine and serotonin), metabolic pathways of drugs (cytochrome CYP450 2D6 and 2C19) and  the human leukocyte antigen system. The paper focuses on some of the major psychotropic drug classes, such as: antipsychotics, antidepressants and mood stabilizers. Validation of statistically significant pharmacogenomics relationships has enabled the development and market approval of some predictive tests which are already integrated into some psychotropic drugs label. Results and discussions. Predictive pharmacogenomics tests have changed the classical approach of prescription  “trial-and error” and “one dose fits all patients” towards personalized therapy. In addition, in new therapeutic candidates’ clinical development, pharmacogenomics practically guides the clinical studies design, by substantially reducing the failure rates, costs and exposure risks of non-responders patients to new drugs. Current translation barriers of predictive pharmacogenomic tests from bench to clinical practice are also discussed. Conclusion. The paper emphasizes the current progress and future prospects in the field of pharmacogenomics as a guide to personalized therapy of psychiatric disorders, by: a) pretreatment selection of the right drug, prescribed in its optimized dose, to the right patient, according to one’s specific genetic biomarkers; b) by improved clinical trials design based on genetic stratification of patients’ population into responders versus non-responders, especially in the costly phases III and IV.